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dc.contributor.author | Bagwan, Navratan | |
dc.contributor.author | Bonzon-Kulichenko, Elena | |
dc.contributor.author | Calvo, Enrique | |
dc.contributor.author | Lechuga-Vieco, Ana V. | |
dc.contributor.author | Michalakopoulos, Spiros | |
dc.contributor.author | Trevisan-Herraz, Marco | |
dc.contributor.author | Ezkurdia, Iakes | |
dc.contributor.author | Rodriguez, Jose Manuel | |
dc.contributor.author | Magni, Ricardo | |
dc.contributor.author | Latorre-Pellicer, Ana | |
dc.contributor.author | Enriquez, Jose Antonio | |
dc.contributor.author | Vazquez, Jesus | |
dc.date.accessioned | 2018-11-05T11:58:21Z | |
dc.date.available | 2018-11-05T11:58:21Z | |
dc.date.issued | 2018 | |
dc.identifier | ISI:000435818300023 | |
dc.identifier.citation | Cell Rep. 2018; 23(12):3685-3697 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/6576 | |
dc.description.abstract | Post-translational modifications hugely increase the functional diversity of proteomes. Recent algorithms based on ultratolerant database searching are forging a path to unbiased analysis of peptide modifications by shotgun mass spectrometry. However, these approaches identify only one-half of the modified forms potentially detectable and do not map the modified residue. Moreover, tools for the quantitative analysis of peptide modifications are currently lacking. Here, we present a suite of algorithms that allows comprehensive identification of detectable modifications, pinpoints the modified residues, and enables their quantitative analysis through an integrated statistical model. These developments were used to characterize the impact of mitochondrial heteroplasmy on the proteome and on the modified peptidome in several tissues from 12-week-old mice. Our results reveal that heteroplasmy mainly affects cardiac tissue, inducing oxidative damage to proteins of the oxidative phosphorylation system, and provide a molecular mechanism explaining the structural and functional alterations produced in heart mitochondria. | |
dc.description.sponsorship | We thank Simon Bartlett (CNIC) for English editing. This study was supported by competitive grants from the Spanish Ministry of Economy and Competitiveness (MINECO) (BIO2015-67580-P) through the Carlos III Institute of Health-Fondo de Investigacion Sanitaria (PRB2, IPT13/0001-ISCIII-SGEFI/FEDER; ProteoRed), by Fundacion La Marato TV3, and by FP7-PEOPLE-2013-ITN ``Next-Generation Training in Cardiovascular Research and Innovation-Cardionext.'' N.B. is a FP7-PEOPLE-2013-ITN-Cardionext Fellow. The CNIC is supported by the MINECO and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO Award SEV-2015-0505). | |
dc.language.iso | eng | |
dc.publisher | Cell Press | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | SPECTROMETRY-BASED PROTEOMICS | |
dc.subject | TANDEM MASS-SPECTROMETRY | |
dc.subject | DATABASE SEARCH TOOL | |
dc.subject | POSTTRANSLATIONAL MODIFICATIONS | |
dc.subject | PEPTIDE IDENTIFICATION | |
dc.subject | SHOTGUN PROTEOMICS | |
dc.subject | QUANTITATIVE PROTEOMICS | |
dc.subject | PHOSPHORYLATION | |
dc.subject | PHOSPHOPROTEOME | |
dc.subject | EXPRESSION | |
dc.title | Comprehensive Quantification of the Modified Proteome Reveals Oxidative Heart Damage in Mitochondrial Heteroplasmy | |
dc.type | journal article | |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 29925008 | |
dc.format.volume | 23 | |
dc.format.page | 3685+ | |
dc.identifier.doi | 10.1016/j.celrep.2018.05.080 | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Fundación La Marató TV3 | |
dc.contributor.funder | Unión Europea. Comisión Europea | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Fundación ProCNIC | |
dc.description.peerreviewed | Sí | |
dc.relation.publisherversion | https://doi.org/10.1016/j.celrep.2018.05.080 | |
dc.identifier.journal | Cell Reports | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Genética Funcional del Sistema de Fosforilación Oxidativa | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Proteómica cardiovascular | |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Proteómica / Metabolómica | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/608027/EU | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/IPT13/0001 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/BIO2015-67580-P | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SEV-2015-0505 | es_ES |
dc.rights.accessRights | open access | es_ES |